ANALYSIS OF THE IMMUNE RESPONSE IN VISCERAL LEISHMANIASIS

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Vaccination using defined antigens has been unsuccessful in leishmaniasis due to an inadequate understanding of the immune events leading to disease. We are pursuing recent findings in the mouse model of leishmaniasis which separate T helper cells into two sub-populations. A clinical protocol is in place in Varanasi, India, to study human bone marrow and splenic aspirates obtained during routine clinical evaluation of patients with visceral leishmaniasis. RNA is prepared and semi-quantitated using RT-PCR to determine the cytokine transcripts in patients with active and cured disease. A grant from the Vaccine Action Programme was recently approved that will fund travel for the US investigators and travel, equipment, supplies, and personnel for the Indian site. The group in Vitoria, Brazil is looking at the potential for the use of IL-12 as an immunomodulator. Lymphocytes from peripheral blood are stimulated in vitro to see if the antigen specific immunosuppression seen in patients with visceral disease can be reversed. Preliminary data indicates human disease parallels the mouse model in some respects. We will continue to develop these sites as potential places for phase III vaccine trials.